R-tolterodine has been shown to reduce bladder pressure in cats and is presently undergoing clinical testing for inhibitory activity in patients suffering from detrusor overactivity (urinary incontinence). R-TOL exerts a spasmolytic effect on bladder smooth muscle by inhibiting the action of acetylcholine on smooth muscle. R-TOL is selective for muscarinic receptors over nicotinic receptors and as a result, no blocking effects are observed at skeletal neuromuscular junctions. Like all other antimuscarinic compounds, R-TOL causes dry mouth, blurry vision, tachycardia and possibly also memory impairment.
R-TOL relaxes urinary bladder smooth muscle and in animals with conditions characterized by increased bladder contractions, cystometric studies have demonstrated that R-TOL has beneficial effects. R-TOL may therefore be useful in the treatment and prevention of incontinency and frequent voluntary urination in patients. The efficacy of R-TOL in the bladder has been attributed to its antimuscarinic effects on the detrusor muscle. Because of its antimuscarinic activity, mydriasis (dilated pupils), xerostomia (dry mouth), tachycardia (fast heart beats) and impaired normal urinary voiding, which mechanisms all involve muscarinic cholinergic receptors, are obvious and reported side effects for R-TOL (Ekstrom et al., J. Urol. 1995, Suppl.4: 394A and Stahl et al. 1995. Neurourol Urodyn 14:647-655).
Pharmacological studies of the individual enantiomers of tolterodine have now been performed and have suggested that the R-TOL indeed is the efficacious enantiomer on muscarinic receptors. Thus, it was concluded that the cholinergic antagonism of racemic tolterodine (RS-TOL) could be attributed mainly to the activity of R-TOL. The rank order of potency of racemic tolterodine and its enantiomers for antimuscarinic activity is: R-TOL was greater or equal to RS-TOL, which was much greater than S-TOL, with S-TOL being approximately one or more orders of magnitude less potent than R-TOL.